[The effect of hypothyroidism on cardiovascular events and type 2 diabetes mellitus developing in rheumatoid arthritis].

AIM: To compare the frequency of cardiovascular events (CVE), to assess the risk of cardiovascular death using the mSCORE and the development of type 2 diabetes mellitus (DM) using the FINDRISC in patients with rheumatoid arthritis (RA) with and without hypothyroidism. MATERIALS AND METHODS: The study included 149 patients (125 women, 24 men) with RA (median age - 57 [52; 61] years). In all patients, traditional factors of cardiovascular risk and glucose metabolism disorders (age, smoking status, total blood cholesterol, blood pressure, overweight, abdominal obesity - AO, heredity burdened by diabetes, insufficient physical activity, the lack of the necessary amount of berries, fruits and vegetables in the daily diet, history of hyperglycemia episodes), the 10-year risk of death from cardiovascular causes according to the mSCORE and the risk of developing type 2 DM according to the FINDRISС were assessed, a history of CVE (myocardial infarctions, and its revascularization, stroke) was recorded. RESULTS: Hypothyroidism was diagnosed in 17.4% of RA patients. Patients with hypothyroidism (group 1) were more likely to have AO and less likely to consume unsufficient dietary fiber than patients with euthyroidism (group 2). Moderate, high and very high risk of development according to the mSCORE and FINDRISC was detected in 61.5% of hypothyroid patients and 48.8% euthyroid patients, according to mSCORE alone - in 30.8 and 44.7%, according to FINDRISC - in 0 and 2.4%, respectively (p>0.05 in all cases); 11.5% of patients in group 1 and 6.5% in group 2 suffered from CVE (OR 1.875, 95% CI 0.462-7.607; p=0.63). CONCLUSION: It is necessary to evaluate the thyroid gland function, especially in patients with AO due to the high frequency of hypothyroidism in RA. Hypothyroidism did not have an independent effect on the severe CVЕ rates, as well as risk assessment according to the score and FINDRISC in RA patients. Theses, with and without hypothyroidism, were predominantly in the moderate, high, very high risk groups according to both scales.

[Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future].

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also "models" for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of "thromboinflammation", which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

[Subclinical atherosclerosis of the carotid arteries in patients with rheumatoid arthritis with low cardiovascular risk].

AIM: To evaluate the detection rate of subclinical carotid atherosclerosis in rheumatoid arthritis (RA) patients with low cardiovascular risk (CVR). MATERIALS AND METHODS: The study included 182 RA patients with low CVR (mSCORE<1%) and no established cardiovascular diseases and a control group comprising 100 people. Atherosclerotic lesion of the carotid arteries was assessed using Doppler ultrasound of the carotid arteries and was determined by the detection of atherosclerotic plaque (ASP) - the local increase in the thickness of the intima-media complex (IMT) >1.5 mm. RESULTS: Carotid ASP were observed more frequently in RA patients with low CVR than in the control group (17% versus 8%; p=0.02). The frequency of ASP in RA patients with low CVR did not depend on the disease's stage or activity and ongoing therapy. In RA, the detection of subclinical atherosclerosis was associated with traditional risk factors: carotid ASP were detected 4 times more often in men than in women (48% versus 12%, p<0.01); carotid IMT correlated with age (R=0.46), body mass index (R=0.17), LDL-C level (R=0.20), systolic blood pressure (R=0.17); p<0.05 in all cases. According to a multivariate model, in RA, the risk of developing ASP increased in the presence of dyslipidemia (odds ratio - OR 2.97; 95% confidence interval - CI 1.36-6.49; p=0.006) and arterial hypertension (OR 2.16; 95% CI 1.03-4.54; p=0.04). In RA patients with carotid ASP, sCD40L level was associated with carotid IMT (R=0.32; p=0.04) and cholesterol concentration (R=0.39; p=0.01). CONCLUSION: Subclinical atherosclerotic lesions of the carotid arteries were observed in 24% of RA patients with low cardiovascular risk and were detected almost 2 times more often than in the control group. In RA patients with low CVR, the risk of developing carotid ASP increased by 2-3 times with concomitant hypertension and dyslipidemia. The carotid IMT was associated with traditional risk factors - age, gender, lipid levels and blood pressure indicators, in cases of detection of ASP - with an immunoinflammatory marker - sCD40L.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Factors of Progression and Occurrence of Atherosclerosis in Rheumatoid Arthritis.

Aim      To determine in a prospective study factors of progressive atherosclerotic lesion of blood vessels in patients with rheumatoid arthritis (RA).Material and methods  This prospective study included 124 patients with RA and suspected ischemic heart disease (IHD) and 30 patients with IHD (comparison group) aged 58 [52; 63] years. On enrollment to the study and at 3 years of follow-up, all patients underwent clinical and instrumental examination according to European and Russian guidelines for diagnosis and treatment of stable IHD (2013), including coronography as indicated. For all RA patients of the comparison group, risk factors (RF) were evaluated, including arterial hypertension, smoking, excessive body weight, family history of cardiovascular diseases (CVD), diabetes mellitus, and dyslipidemia. The following laboratory data were evaluated: blood count; biochemistry, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), rheumatoid factor (RhF), cyclic citrullinated peptide antibodies, and high-sensitivity C-reactive protein (hsCRP). Proinflammatory cytokines, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α (TNF- α), were measured in RA patients once, at 3 years of follow-up.Results Incidence of FRs for CVD was similar in RA patients and in the comparison group. Median RA duration before inclusion into the study was 11 years, and median DAS28 index score was 3.8. Incidence of dyslipidemia due to increased TC, LDL-C, and HDL-C was higher for RA patients at baseline. The LDL-C goal (<1.8 mmol/l) was achieved only in 3 (10 %) patients of the comparison group and 10 (8 %) RA patients. RA patients had higher levels of the inflammation indexes, hsCRP (0.75 mg/dl vs. 0.16 mg/dl; p<0.05) and erythrocyte sedimentation rate (ESR) (15 mm/h vs. 11.5 mm/h; p<0.05). In the RA group at baseline, atherosclerotic plaques with carotid artery (CTA) stenosis of 20% or more were found in 94 (77 %) patients; in 3 of them, CA stenosis was >50%. Patients with RA frequently had unchanged or slightly changed coronary arteries (CA) (47% of patients), and less frequently they had hemodynamically significant multi-arterial coronary atherosclerotic lesions (7 % vs. 57 % of patients in comparison group). At 37.5 months, 21 (23 %) of 94 RA patients had progressive atherosclerosis in CA and/or CTA; 12 (13 %) RA patients had only progressive CA atherosclerosis; 7 (8 %) had only progressive CTA atherosclerosis; and 2 (2 %) had simultaneous progression of CA and CTA atherosclerosis. Two groups of RA patients were formed, with the progression of atherosclerosis (n=21) and without the progression of atherosclerosis (n=69). RFs for the development/progression of atherosclerosis in RA patients included smoking, family history of CVD, and duration of the disease. Levels of lipids did not differ. Levels of proinflammatory cytokines (IL-1ß, IL-6, TNF-α) were higher in RA patients with progressive atherosclerosis. No effects of the anti-rheumatic therapy on the progression of atherosclerosis were observed.Conclusion      Progression of atherosclerosis in RA remains in disease with low and moderate activity during the anti-rheumatic and hypolipidemic treatment. The development of atherosclerosis in RA is determined by lipid, inflammatory, and immune disorders.

[Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis].

AIM: To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. RESULTS: High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. CONCLUSION: RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

[Level of N-terminal fragment of brain natriuretic peptide progenitor and atherosclerotic damage of brachocephalic arteries in patients with rheumatoid arthritis with inefficiency and/or injurability of basic anti - inflammatory treatment].

The high prognostic significance of the concentration of the N-terminal - pro-B-type natriuretic peptide (NT-proBNP) in the development of cardiovascular diseases (CVD) was identified for rheumatoid arthritis (RA) and general populations. AIM: to investigate the significance of NT-proBNP level in patients (pts) with RA with the ineffectiveness and/or intolerance of basic anti - inflammatory therapy; compare the level of NT-proBNP with atherosclerotic lesion of the brachiocephalic arteries (BCA), traditional risk factors and inflammatory markers. MATERIALS AND METHODS: The investigation enrolled 28 pts (24women/4men) with the lack of efficacy/resistance and/or intolerance of basic anti - inflammatory drugs (DMARDs); median age was 55 [46; 61] years, median disease duration 114 [60; 168] month; DAS28 6,2 [5.1; 7.0]; SDAI 35.0[23.9; 51.0], CDAI 30.0[21.0; 42.0], serum positivity for rheumatoid factor (RF) (100%)/anti - cyclic citrullinated peptide antibodies (ACCP) (86%). The study did not include RA pts with congestive heart failure. High incidence of traditional risk factors was found in RA pts: arterial hypertension - in 75%, dyslipidemia - 61%, smoking - 17%, overweight - 61%, family history of cardiovascular diseases - 36%, hypodynamia - 68%. Coronary artery disease was diagnosed in 11% RA pts. Lack of efficacy of 3 or more DMARDs was found in 46% of pts, intolerance to previous therapy with DMARDs - in 54% pts. 47% were receiving methotrexate (20 [18; 25] mg/week), 11% - leflunomide, 7% - sulfasalazine, 46% - glucocorticoids, 75% - non - steroidal anti - inflammatory drugs. The control group consisted of 20 healthy donors, comparable to pts by age and sex. Serum levels of of NT-proBNP were measured using electrochemiluminescence method Elecsys proBNP II (Roche Diagnostics, Switzerland). The determination of the intima - media thickness (IMT) BCA were assessed from duplex scanning. Atherosclerotic lesion of BCA was assessed by the presence of atherosclerotic plaque (IMT ≥1.2 mm). RESULTS: NT-proBNP concentrations in RA pts proved to be higher (78.7 [41.4; 101.3] pg/ml) than those in the control group (55.3 [36.6; 67.3] pg/ml, p100 pg/ml - 1 group (n=6) and ≤100 pg/ml - 2 group (n=22). Groups of RA pts did not differ in gender, age, activity of RA, frequency of detection of traditional risk factors. Atherosclerotic lesion of the BCA was detected in 3 (50%) pts of the 1 group and in 8 (36%) pts of the 2 group (p>0.05). In RA pts the level of NT-proBNP correlated with age (r=0.39; p.

[Clinical value of multiplex immune assay of antinuclear antibodies in systemic lupus erythematosus.]

A promising trend in the diagnosis of systemic autoimmune diseases is the multiplex immune assay (MIA) of autoantibodies and other laboratory biomarkers using microchips. The aim of the work was to study the diagnostic and prognostic significance of MIA antinuclear antibody (ANA) profiles in systemic lupus erythematosus (SLE). 94 patients with SLE, 70 patients with other rheumatic diseases and 30 healthy donors were examined. ANA (antibodies to doublestranded - dsDNA, Sm, SS-A/Ro, SS-B/La antigens, nucleosomes, ribosomal protein P-RibP and ribonucleoprotein - RNP-70) were determined in the serum by MIA using the xMAP technology. In MIA, antibodies to dsDNA, Sm and RibP have a high diagnostic specificity (Sp) (95.0-99.0%) and a likelihood ratio of positive results (LR+) (9.67-15.0), i.e. are the most "useful" diagnostic tests, and antibodies to RNP-70, SS-A/Ro and nucleosomes are classified as "useful" tests for the diagnosis of SLE (Sp: 84.0-95.0%, LR+> 2.0). Determination of profiles from 3 or more antigen-specific ANA by MIA increases the Sp method to 98.0-100%, and the LR+ - to the maximum values. Profiles from 7 subpopulations of ANA (antibodies to dsDNA, Sm, RibP, SS-A/Ro,SS-B/La, nucleosomes and RNP-70, 57.9%, 71.9%, 82.5%, 61.4 %, 84.2%, 50.9%, 84.2%) were found in the chronic variant of SLE. In the acute course of the disease, 4 subpopulations of ANA are simultaneously detected (antibodies to dsDNA, Sm, SS-A/Ro and nucleosomes, 77.3%, 45.5%, 40.9% and 72.7%); in subacute course there are 2 subpopulations of ANA (antibodies to dsDNA and nucleosomes, 53.3% and 46.7%). The activity index of SLEDAI-2K positively correlates with the concentration of antibodies to dsDNA (r = 0.55, p < 0.05), nucleosomes (r = 0.65, p < 0.05), RibP (r = 0.32; p < 0.05) and Sm (r = 0.36, p < 0.05) in the blood. There was no reliable relationship between the production of varieties of ANA and the index of organ damage. Mucocutaneous disorders, lupus-nephritis and neurolupus were most often associated with the detection of antibodies to dsDNA (53.2-64.0%), nucleosomes (55.3-66.0%), SS-A/Ro (38.0-40.4%) and Sm (27.8-36.2%). MIA of ANA profiles is an important tool for implementing a personalized approach to diagnosis, evaluation of activity, course and clinical and immunologic subtypes of SLE.

Atherosclerosis: perspectives of anti-inflammatory therapy.

According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1ß (IL-1ß), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1ß determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1ß by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1ß determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1ß by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1ß canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CАNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

[Behçet's disease: Intracardiac thrombosis (a description of two cases and a review of literature)]. / Bolezn' Bekhcheta: vnutriserdechnyi tromboz (opisanie dvukh nabliudenii i obzor literatury).

Behçet's disease (BD) is systemic vasculitis of unknown etiology, which is more common in the countries located along the Great Silk Road. The disease is diagnosed if a patient has 4 key diagnostic signs: aphthous stomatitis, genital sores, and eye and skin lesions. Vascular diseases referred to as minor criteria for BD are characterized by the formation of aneurysms and thrombosis, predominantly in the venous bed. In venous disorders, a blood clot can form in any vessel, including caval, cerebral, pulmonary, and other veins. The paper describes two clinical cases of BD with intracardiac thrombosis. In one case, a 24-year-old male patient with a documented diagnosis of BD, echocardiography revealed a left ventricular spontaneous echo contrast phenomenon that disappeared due to immunosuppressive therapy. The other case was a 34-year-old female patient, in whom the diagnosis was based on the international disease criteria: aphthous stomatitis, skin lesions (pseudopustulosis, erythema nodosum), and genital sores. Computed tomographic angiography showed a 3.7×2.2-cm mass (thrombus) in the right atrium. In addition, blood clots were present in the hepatic and inferior vena cava. No abnormalities in the coagulation system were found in both cases.

[THE CLINICAL INFORMATIVENESS OF AUTOMATED METHODS OF SCREENING DETECTION OF ANTI-NUCLEAR ANTIBODIES USING INDIRECT REACTION OF IMMUNE FLUORESCENCE, ENZYME-LINKED IMMUNOSORBENT ASSAY AND MULTIPLEX XMAP TECHNOLOGY UNDER SYSTEMIC LUPUS ERYTHEMATOSUS].

Thew antinuclear antibodies (ANA) consist heterogeneous group of auto antibodies reacting with various components of nucleus and cytoplasm. The ANA is a main serological marker of systemic lupus erythematosus (SLE). The implementation in clinical practice of new highly productive techniques of immune analysis using automated systems sets up prerequisites for standardization and amelioration of reproducibility of detection of ANA. The study was carried out to compare diagnostic significance of automated techniques of screening detection of ANA (indirect immunofluorescence test on cells HEp-2 (IIFT-HEp-2)), enzyme-linked immunosorbent assay (ELISA) and multi-complex immune analysis (MIA, using suspension technology xMAP) in serum of patients with SLE. The serums from 94 patients with SLE were analyzed. The comparison group included 70 patients with other rheumatic diseases. The control group consisted of 30 healthy donors. The screening detection of ANA using technique IIFT-HEp-2 was implemented on automated platform AKLIDES, ELISA - on automated analyzer ALEGRIA and MIA on automated analyzer BioPlex 2200. The technique IIFT-HEp-2 demonstrated the most high diagnostic sensitivity as compared with ELISA and MIA- BioPlex 2200 (96.8%; 79.8% and 82.9% correspondingly). The general diagnostic specificity of detection of ANA using technique IIFT-HEp-2 was lower than in case of ELISA and MIO-BioPlex 2200 (40%, 70% and 57% correspondingly). In the group of healthy donors the lowest diagnostic specificity was observed in ANA screening analysis using MIA-BioPlex 2200 (80%) while in case of applying IIFT-HEp-2 and ELISA indices of diagnostic specificity made up 93.3% and 96.7% correspondingly. The ANA analysis of mix of 26 nuclear antigens using ELISA technique was a reliable laboratory test for diagnostic of SLE (likelihood ratio of positive result - 2.66). By the level of likelihood ratio of negative result of the IIFT-HEp-2 technique was more informative test for exclusion of diagnosis of SLE than techniques of ELISA and MIA-BioPlex 2200 (0.08; 0.29 and 0.3 correspondingly). The detection of ANA using technique of is the most preferable primary screening test for diagnostic of SLE. The ELISA of antibodies to mix of nuclear antigens and MIA on the basis of xMAP technology are less preferable screening tests for diagnostic of SLE as compared with IIFT-HEp-2 because of false-negative results in 20% and 17% of cases correspondingly. ELISA and MIA are to applied as confirmatory screening tests permitting to detect antigen-specific ANA in patients with SLE with positive results of IIFT-HEp-2.

[Cardiovascular disease in rheumatic diseases].

The representatives of immunoinflammatory diseases are rheumatic ones, such as primarily rheumatoid arthritis, juvenile idiopathic arthritis, spondyloarthritis, psoriatic arthritis, systemic lupus erythematosus, and other systemic connective diseases, which are characterized by a high risk for untimely death. The high risk of untimely death in these diseases has been found to be associated with the severity of an immunoinflammatory process that gives rise to severe irreversible damage to vital organs and systems and with the development of a wide spectrum of comorbidities (infections, interstitial lung disease, malignant tumors, osteoporotic fractures, etc.). Among them, diseases of the cardiovascular system, which are most commonly caused by the early development and.accelerated progression of atherosclerotic coronary lesions, hold a central.position. The paper gives the data available in the recent literature on the impact.of antirheumatic therapy (disease-modifying antirheumatic drugs and biological agents) on' the cardiovascular system.

[Interleukin-6 inhibition and cardiovascular disease in patients with rheumatoid arthritis].

Rheumatoid arthritis (RA) is a' disease conferring high risk for cardiovascular events (CVE). Systemic inflammation underlying RA favors development of CVE. The safety of biological agents, acting on the cardiovascular system has been inadequately investigated. On the one hand, they decrease RA activity and, on the other, may increase the risk of CVE. This review analyzes' the literature data predominantly published in recent years on the effect of an IL-6 receptor inhibitor on the cardiovascular system. Tocilizumab is shown to be a promising agent to reduce cardiovascular risk the findings need to be clinically verified. Long-term prospective investigations should be conducted to determine more exactly the impact of IL-6 receptor inhibition on. the development of CVE.

[N-terminal pro-brain natriuretic peptide levels and diastolic dysfunction in patients with early rheumatoid arthritis before the administration of disease-modifying antirheumatic drugs].

AIM: To determine N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in patients with early rheumatoid arthritis (RA) before the use of disease-modifying antirheumatic drugs (DMARDs); to compare NT-proBNP values with traditional risk factors (TRF), cardiovascular diseases (CVD), inflammatory markers, and left ventricular (LV) diastolic dysfunction (DD). SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid RA diagnosis (the 2010 ACR/EULAR criteria), 56 (74%) women, median (Me) age, 54 years; disease duration, 7 months; seropositive for IgM rheumatoid factor (87%) and/or anti-cyclic citrullinated peptide antibodies (100%) with no history of the use of DMARDs and glucocorticosteroids. Duplex scanning and echographic findings were used to assess TRF for CVD and carotid artery atherosclerosis (CAA) in all the patients with early RA prior to therapy. An E/A ratio was used as a criterion for LVDD. RESULTS: NT-proBNP concentrations in patients with early RA proved to be higher than those in the control group (p<0.0001). Higher-than-normal NT-proBNP levels were seen in 36 (49%) patients. The patients with early RA and elevated NT-proBNP values were older and had a higher body mass index (BMI) than those with normal NT-proBNP levels. Those with elevated NT-proBNP concentrations were more frequently found to have CAA, coronary calcification, and coronary heart disease; their intima-media thickness was also larger and C-reactive protein (CRP) levels higher than in those with normal NT-proBNP values. There were correlations between NT-proBNP levels and erythrocyte sedimentation rate, CRP, simplified disease activity index, and clinical disease activity index. Multivariate analysis revealed that chronic heart failure (CHF), CAA, CRP and low-density lipoprotein (LDL) levels, and BMI correlated with NT-proBNP concentrations. LVDD was detected in 35 (48%) patients with early RA. The level of NT-proBNP in patients with DD was higher than in those without DD. Higher-than-normal NT-proBNP values were observed in 23 (65%) and 12 (32%) patients with and without LVDD, respectively. The optimal NT-proBNP level for CHF detection was equal to 237.4 pg/ml (86% sensitivity and 85% specificity); the area under the ROC curve was 0.879. CONCLUSION: Just at the early disease stage, the patients are noted to have a high NT-proBNP level that is influenced by higher BMI, low LDL levels, CAA, CHF, and high CRP values. In the patients with early RA, the diagnostically significant NT-proBNP concentration for CHF detection was higher (237 pg/ml) than in those without RA (125 pg/ml). The patients with early RA should undergo NT-proBNP determination, LVDD screening, correction of TRF for CVD, atherosclerosis treatment, and remission achievement.

[Cardiovascular Complications of Rheumatoid Arthritis: Prevalence and Pathogenesis].

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with high risk of cardiovascular events. Among main causes of death in RA are: myocardial infarction, cerebrovascular accident, sudden cardiac death, which are determined by the early development and rapid progression of atherosclerotic vascular lesions. According to studies high risk of cardiovascular events is not explained by only classical risk factors. It is assumed that there are additional mechanisms of development of adverse outcomes such as systemic inflammation, increased arterial stiffness, and endothelial dysfunction. In this literature review we present various risk factors of cardiovascular events in patients with RA and their relation to RA pathogenesis.

[Left and right ventricular diastolic dysfunction in patients with early rheumatoid arthritis before prescribing disease-modifying antirheumatic therapy].

AIM: To estimate the rate of diastolic dysfunction (DD) of the left and right ventricles (LV and RV) in patients with early rheumatoid arthritis (RA) before using disease-modifying antirheumatic drugs (DMARDs) therapy and to investigate its association with traditional risk factors (TRFs) for cardiovascular diseases (CVD) and inflammatory markers. SUBJECTS AND METHODS: The investigation enrolled 74 patients with a valid diagnosis of RA, including 56 (74%) women (median age, 54 years; disease duration, 7 months); the patients who were seropositive for rheumatoid factor (RF) (87%) and/or anti-cyclic citrullinated peptide (anti-CCP) antibodies (100%) who had not been on DMARDs or glucocorticosteroids. TRFs for CVD and carotid artery atherosclerosis were assessed from duplex scanning data and echocardiography was performed in all the patients with early RA before starting the therapy. The ratio of the maximum blood flow velocity during early diastolic filling (E) to that during atrial systole (A) was used as a criterion for LVDD and RVDD. There were 3 types of impaired ventricular filling: 1) E/A <1; 2) E/A = 1-2; 3) E/A > 2. RESULTS: LVDD and RVDD were detected in 35 (48%) and 17 (23%) patients, respectively. RVDD was recorded only in conjunction with LVDD. Among LVDD and RVDD, the former was prevalent. All the patients with early RA were divided into 3 groups: 1) patients with LVDD and RVDD; 2) those with LVDD; 3) those without ventricular DD. All the three groups were matched for the level of DAS28, anti-CCP antibodies, and RF. The incidence of arterial hypertension, dyslipidemia, and abdominal obesity was higher in the patients of Groups 1 and 2 than in those of Group 3. There was a progressive decrease in high-density lipoprotein (HDL) cholesterol concentrations and increases in triglyceride (TG) levels and atherogenic index from Group 3 to Group 1, with the concentrations of total cholesterol and low-density lipoprotein cholesterol being similar in the 3 groups. Coronary heart disease was recorded more frequently in Group 2 than in Group 3. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) proved to be also significantly higher in the patients with DD than in those without DD. Correlations were found between LV E/A and ESR, CRP, HDL cholesterol, TG, RV E/A and ESR, DAS28, TG. CONCLUSION: The patients with early-stage RA were found to have high incidence rates of LVDD and RVDD, which is related to the high prevalence of CVD, the high spread of TRF for CVD, and the high activity of an inflammatory process.

[The clinical informativeness of detection of antibodies to citrullinated proteins under rheumatoid arthritis].

The main diagnostic laboratory markers of rheumatoid arthritis are IgM rheumatoid factor and antibodies to citrullinated proteins. The IgM rheumatoid factor is a sensitive but insufficiently specific marker of rheumatoid arthritis. The antibodies to citrullinated proteins have a higher specificity for diagnostic of rheumatoid arthritis. The antibodies to cyclic citrullinated peptide and modified citrullinated vimentin are the main representatives of family of antibodies to citrullinated proteins applying in clinical diagnostic practice. The study was carried out to deternine the role of antibodies to citrullinated proteins and modified citrullinated vimentin in diagnostic, evaluation of activity and severity of destructive alterations under rheumatoid arthritis. The samplings of 993 patients with reliable diagnosis of rheumatoid arthritis. 179 patients with other rheumatoid diseases and 30 healthy donors were examined. The measurement of serum concentration of IgM rheumatoid factor and C-reactive protein was implemented by immune nephelometric analysis and antibodies to citrullinated proteins were analyzed by enzymoimmunoassay The erythrocyte sedimentation rate was established using the Westergreen technique. It was established that antibodies to modified citrullinated vimentin had the highest diagnostic specificity (83%), antibodies to cyclic citrullinated peptide had the highest diagnostic specificity (87%). The diagnostic specificity of joint detection of IgM rheumatoid factor, antibodies to citrullinated proteins and antibodies to modified citrullinated vimentin made up to 87%. In patients negative to rheumatoid factor the rate ofdetection of antibodies to citrullinated proteins made up to 34% and antibodies to modified citrullinated vimentin made up to 48%. The diagnostic effectiveness of detection of antibodies to citrullinitted proteins (ratio of likelihood of positive and negative results of test was correspondingly 5.5 and 0.3; area under ROC curve 0.8) and antibodies to modified citrullinated vimentin (ratio of likelihood of positive and negative results of test was correspondingly 4.4 and 0.2; area under ROC curve 0.9) surpassed the same in analysis of IgM rheumatoid factor (ratio of likelihood of positive results--3.2, ratio of likelihood of negative results--0.4, area under ROC curve--0.8). The weak positive correlation relationship was established between concentration of antibodies to cyclic citrillinatedpeptide/antibodies to modified citrullinated vimentin in blood serum and indicators of clinical laboratory activity of rheumatoid arthritis (ESR, CRP DAS 28, (r-0.2. p < 0.05). The high positive levels of antibodies to modified citrullinated vimentin associated with expressed destructive affection of joints (p < 0.02). The antibodies to cyclic citrullinated peptide are the most highly specific and clinically informative laboratory diagnostic marker of rheumatoid arthritis. The detection of antibodies to modified citrullinated vimentin is an important additional serological test to diagnose rheumatoid arthritis in IgM rheumatoid factor-negative and/or antibodies to cyclic citrullinated peptide-negative patients and to forecast severe destructive affection of joints under the given disease. The joint study of IgM rheumatoid factor, antibodies to cyclic citrullinated peptide and antibodies to modified citrullinated vimentin under rheumatoid arthritis has higher diagnostic sensitivity as compared with isolated antibodies to citrullinated proteins.

[Cardiovascular diseases in patients with rheumatoid arthritis during long-term methotrexate therapy].

AIM: To compare the prevalence of risk factors, clinical and subclinical manifestations of cardiovascular diseases (CVD) and their complications in methotrexate (MT)-treated and untreated patients with rheumatoid arthritis. SUBJECTS AND METHODS: The investigation enrolled 193 patients (168 women and 25 men) less than 60 years of age (mean age 49 [44; 53] years) with RA. The patients were divided into 2 groups: 1) 69 patients who received MT in a dose of 15.1 [10.2; 21] mg/week for at least 12 months (mean disease duration 25 [18; 48] months); 2) 124 patients who did not take MT. The patient groups were matched for age, gender, disease duration, RA activity, and the rate of rheumatoid factor (RF) seropositivity and extraarticular manifestations. RESULTS: Dyslipidemia was significantly less frequently identified in MT-treated patients (35/69 or 51%) than in MT-untreated ones (85/124 or 69%; p = 0.01). The serum from the patients treated with MT exhibited higher high-density lipoprotein cholesterol concentrations ((1.8 [0.9; 2.0] mmol/l) than in those untreated with MT (1.2 [1.0; 1.6] mmol/l; p = 0,047). In Group 1, hypertension (49%) and diabetes mellitus (3%) were slightly rare than in Group 2 (62 and 13%, respectively; p > 0.05). Carotid atherosclerotic plaques were found in 19 and 16% and intima-media thickness (IMT) enlargement was seen in 53 and 56% of the patients in Groups 1 and 2, respectively. Silent myocardial ischemia was diagnosed in every 10 patients; heart disease (exertional angina, myocardial infarction) was in every 5 patients in both groups. Aortocoronary bypass surgery was performed in 2 (3%) patients from those who received MT and had experienced MI and in one (1.6%) patient from the MT-untreated group. CONCLUSION: Long-term MT therapy was associated with the lower rate of dyslipidemia, but it failed to affect the incidence of CVD in patients with RA.

[The role of adipose tissue in rheumatoid arthritis].

AIM: To estimate the frequency of obesity in a Russian cohort of patients with early rheumatoid arthritis (RA), determine adipocytokine (adiponectin, leptin) levels and their relation to RA activity. MATERIALS AND METHODS: 47 patients with early RA fulfilling ACR/EULAR(2010) criteria and using no BAID or GC. Mean age 57 [47;62] yr, duration of disease 7 [4;8] yr, median of DAS28 5.9 [5.3; 69]. Control group included 30 age-matched healthy donors. The degree of obesity was assessedfrom metabolic syndrome criteria (NCEP/ATPIII, RSSC, WHO); leptin and adiponectin were measured by ELISA, the L/A ratio was calculated. RESULTS: Patients with RA had the same mean BMI but greater waist circumference (WC) and waist/hip ratio than controls (p=0.003 and p = 0.04). Obesity was diagnosed in 63.8 and 40% of the patients in these groups (p=0.04) based on NCEP/ ATPIII criteria and in 65.9 and 40% respectively by WHO criteria. The occurrence of obesity by RSSC criteria was not significantly different (p = 0.9). In patients with RA adiponectin level was higher (p=0.04) while leptin level and L/A ratio lower (p=0.02 and 0.003) than in controls. BMI correlated with ESR, CRB, DAS28, leptin and L/A (p<0.05) in both groups. ESR positively correlated with leptin level andA/L but negatively with adiponectin level (p<0.05). CONCLUSION: The study showed high prevalence ofobesity in patients with early RA and its relation to inflammation. It was associated with increased serum adiponectin level, decreased leptin level and insulin resistance.

[The comparative evaluation of the diagnostic value of methods of detection of antibodies to citrullinized proteins under rheumatoid arthritis].

The hyper production of large specter of autoantibodies, primarily rheumatoid factors and antibodies to citrullinized proteins, is a characteristic sign of rheumatoid arthritis. The detection of these antibodies plays an important role in diagnosing the disease, especially on its early stages. The study compared the diagnostic accuracy of different methods of detection of antibodies to citrullinized proteins under rheumatoid arthritis. The examined sample included 144 patients aged 33-58 years with reliable diagnosis of rheumatoid arthritis. The patients with systemic lupus erythematous, osteoarthritis, psoriatic arthritis, OVERLAP syndrome, ankylosing spondylitis and conditionally healthy donors consisted the comparative group. To detect antibodies to citrullinized proteins the methods of enzyme immunoassay, electrochemiluminescence, immunochromatography were applied. The study demonstrated that all the methods of detection of antibodies to citrullinized proteins have adequate diagnostic value to be implemented both in a routine clinical diagnostic practice and on the stage of screening of patients.